ABSTRACT This Research Specialist proposal will support my 2 main roles in my Unit Director's (Nima Sharifi, M.D.) research program. My primary role is focused on laboratory management, animal model (mouse) projects, and clinical studies in my Unit Director's laboratory, while my secondary role is as Program Manager for the Genitourinary Malignancies Research Center (GUMRC), which is led by my Unit Director. For the Unit Director's laboratory in addition to maintaining safety and compliance of all research personnel, I am essential to the advancement of laboratory techniques, diagnostic tools and critical planning required to meet the goals of our NCI-funded and other cancer research. I am significantly involved in all in vivo animal model work including preparation and submission of all protocols to the Institutional Animal Care and Use Committee (IACUC), as well as the surgical and technical portions of the experiments. I am instrumental in training our unit's personnel (clinical fellows, residents, postdocs, technologists and students) in these critical techniques (both in vivo and lab based) in an effort to maintain scientific congruence while ensuring that laboratory personnel adhere to IACUC, Institutional Review Board and Institutional Biosafety Committee rules and regulations. For my Unit Director's laboratory, our primary focus remains on prostate cancer. While treatment of localized disease results in favorable outcomes, metastatic prostate cancer remains incurable. The frontline treatment for advanced metastatic prostate cancer is medical or surgical castration to reduce androgen hormone levels, referred to as androgen deprivation therapy (ADT). When successful, ADT reduces intratumoral androgens, resulting in absence of androgen receptor (AR) signaling. However, these tumors commonly develop ADT-resistance and are termed castration-resistant prostate cancer (CRPC). Our research goals focus on how prostate cancer cells can produce their own steroids in response to ADT, thus leading to cancer progression. By understanding the foundations of CRPC and the mechanisms that drive therapeutic resistance, we aim to identify new drug targets and treatments for diagnosis and treatment. For my Unit Director's clinical studies and extending into our GUMRC, I participate in study conceptualization and function as the intermediary between the Unit Director and our clinical collaborators. The GUMRC is focused on basic and translational studies of GU malignancies (prostate, bladder, and kidney). The center is an inter-disciplinary translational partnership that leverages Cleveland Clinic's research and clinical strengths to accelerate bench-to-bedside therapeutic discoveries. This Research Specialist award will allow me to 1) continue to provide my expertise in study design and technical skills for current and future NCI-funded GU projects, as well as to develop innovative methods to better achieve our goals, and 2) develop greater knowledge and the skills needed for effective program coordination and management that will enable our GUMRC to make rapid and influential advances in the treatment of GU malignancies.